DNA and the Nobel Prize: The History of the Discovery of DNA Structure

00:00:06.06 So my name is Erling Norrby, and I am trained to be a virologist, 00:00:11.29 and I have taught about viruses at the medical school 00:00:16.10 but also I have overriding administrative responsibilities 00:00:19.27 both at the Karolinska Institute, the school of medicine in Stockholm, 00:00:23.16 and the Royal Swedish Academy of Sciences in Stockholm. 00:00:27.02 And the story I am going to tell you about is the 00:00:31.21 discovery of the structure of DNA. 00:00:34.01 And to those of you in the audience who are a little younger would think 00:00:38.19 but the structure of DNA... that has been known forever. 00:00:42.06 But that is not so. 00:00:43.11 So, there was a true discovery of the structure and as a consequence of that, 00:00:49.07 one also started understanding the enormous impact 00:00:52.06 that this molecule had. 00:00:53.23 Before this discovery, it was not known. In fact, there was considerable debate 00:00:58.21 on the relative role of proteins versus nucleic acids, 00:01:04.11 and the emphasis was on the proteins because the proteins 00:01:07.11 have much more diversity, 20 amino acids that could be varied indefinitely. 00:01:11.17 Whereas the DNA was a rather boring molecule with just four nucleotides 00:01:16.00 and there were also some incorrect data suggesting that the relative representation 00:01:23.13 of the 4 bases was rather constant in different types/kinds of DNA. 00:01:28.10 So how was this discovery made? 00:01:31.09 Well, what happened was that in the 1940s, the development 00:01:36.20 of the field of physics had been very, very powerful, 00:01:40.10 and physicists thought that they might have something to contribute to the field of biology. 00:01:45.01 So a lot of physicists trained to understand the major questions in biology at the time, 00:01:53.12 and they started to study biological phenomena. 00:01:57.02 In England, the Medical Research Council decided to really invest in it 00:02:02.21 to stimulate physicists to study biological phenomena. 00:02:06.02 And there were two centers that were established. 00:02:09.00 One was at the Cavendish Laboratory, Cambridge, 00:02:12.16 and that was managed by Lawrence Bragg. 00:02:15.10 He became the head of that institution in the early 1930s. 00:02:20.01 And the other was at King's College in London. 00:02:26.10 And the person who was in charge there was John Randall 00:02:31.04 who had during the war made... (He was a physicist) 00:02:36.11 made very important contributions to the development of the RADAR 00:02:42.02 that was very critical in deciding the outcome of the Second World War. 00:02:46.24 But there was a kind of gentlemen's agreement between these two different laboratories, 00:02:53.02 and also supported by the Medical Research Council, 00:02:56.18 namely that in Cambridge one would study protein structure, 00:03:00.09 and that King's College they wanted to study other structures, 00:03:03.07 including nucleic acids. 00:03:05.02 And the two leading figures at the Cavendish laboratory was Max Perutz and John Kendrew. 00:03:12.11 They were crystallographers who really embarked on an almost impossible project 00:03:21.16 namely to study very huge molecules with a complexity 00:03:27.00 that one predicted that it could not be done. 00:03:31.11 But they started this in the early '30s, 00:03:34.09 and then they developed this technique step by step, 00:03:40.00 way into the 1950s, and then later in the '50s came much better computers. 00:03:46.19 And that should be emphasized that the possibility 00:03:49.20 of processing huge amounts of information helped in this analysis. 00:03:54.22 And eventually one managed to define the three dimensional structure of very complex 00:03:59.24 protein structures like hemoglobin and myoglobin. 00:04:03.11 So that was the protein studies. 00:04:05.16 But at the King's College, there was a person called Maurice Wilkins, 00:04:12.22 who had joined Randall already before he came to King's College 00:04:18.02 at St. Andrew's in Scotland. 00:04:20.17 And he was trying to study nucleic acids. 00:04:23.25 In January 1951, he was joined by a female scientist by the name of Rosalind Franklin 00:04:30.22 who came from France where she studies inorganic carbon compounds. 00:04:37.08 She had very little knowledge about biology. 00:04:41.20 And she was given this task to help or to study DNA, 00:04:47.06 and then she thought that the mission was to do it on her own responsibility. 00:04:51.23 Wilkins thought that they should do it as a collaboration. 00:04:55.05 But they never developed the collaboration between these two persons. 00:04:58.24 And there's very special stories about how they each one of them, 00:05:06.17 tried to approach this problem. 00:05:09.03 What really turned the whole thing was when in Autumn of 1950, 00:05:16.00 Jim Watson came to Cambridge. 00:05:19.23 It's a long story of why he ended up there, because he was on scholarship in Denmark. 00:05:23.05 but he was dissatisfied with that, and he had this idea 00:05:26.27 that he thought that DNA had something to do with the genetic material. 00:05:31.09 And he was a little obsessed by that. 00:05:33.02 And then he was in 1950, he was in Naples and heard 00:05:38.06 a lecture by Wilkins about the attempts to study the structure of DNA 00:05:43.15 by crystallographic analysis, and that further convinced him that this was the thing to do. 00:05:51.07 But he was not satisfied with his time in Denmark, 00:05:55.05 so with some help from his mentors, he could move to the Cavendish laboratories. 00:06:01.11 And who did he meet there? 00:06:04.03 He met Francis Crick. Francis Crick was about 12 years older 00:06:06.29 than what Jim Watson was, but the two of them really formed a remarkable couple, 00:06:13.00 and they stimulated each other. 00:06:14.19 And even though the Cavendish laboratory was supposed to work on proteins, 00:06:19.15 then these two gentlemen couldn't refrain 00:06:22.02 from discussing nucleic acid and its possible structure. 00:06:26.10 And they even made a little model of that, 00:06:28.22 that was then described to them to be completely wrong. 00:06:34.04 They had a triple helix. They had bases extending into the periphery. 00:06:38.07 And it was heavily criticized. Clearly it was wrong. 00:06:43.06 And then Bragg decided that they were not allowed to work on nucleic acids. 00:06:48.26 But one can see in the documents that there are that they kept on thinking about that. 00:06:55.09 They met Chargaff, the famous person who had already at this time 00:07:01.02 said that the amount of nucleotides, 00:07:02.24 A and T and G and C, that they are in equal proportion in each of these pairs. 00:07:10.04 And no one had fully understood why this was important. 00:07:12.12 So anyhow Watson and Crick, they were not allowed to work on the nucleic acid, 00:07:19.23 but then things started to happen because Linus Pauling had had a fantastic advance. 00:07:26.07 He was the giant in chemistry of his time. 00:07:29.03 He won the Nobel prize in '54 for his studies of the chemical bond. 00:07:32.20 But all of that time he had a higher contribution in terms of the structure of proteins 00:07:38.14 particularly the alpha- helix. 00:07:41.18 And that was a little to the chagrin of the Cavendish group, 00:07:45.21 because they would have liked to be ahead of Pauling. 00:07:48.13 And then Pauling decided no, I am going to go for the holy grail. 00:07:52.00 I am going to study the structure of DNA. 00:07:54.12 And the rumors started to spread, 00:07:58.17 in '52 it was. And then Linus Pauling's son, Peter Pauling, was at the Cavendish laboratory. 00:08:08.11 And so he received all the information from his father, 00:08:11.00 and in around December 1952 there was a manuscript from Pauling, 00:08:18.09 about the structure of DNA, and of course Watson and Crick 00:08:21.18 got all very, very concerned, because maybe Pauling had really solved the structure. 00:08:28.07 They started to look at his manuscript, and to their big surprise, 00:08:32.09 they found that this giant in chemistry had made some major, major mistakes. 00:08:37.27 In fact, the model he proposed was very similar 00:08:40.17 to the model that Watson and Crick had proposed a year before. 00:08:43.11 And had been demonstrated to them to be all wrong. 00:08:46.09 This related to what Bragg said because scientists are competitive, 00:08:55.04 and he wouldn't like to see Pauling coming ahead in his field. 00:09:00.12 So he said to Watson and Crick, okay, you can work on DNA. 00:09:03.11 That was about Christmas time in 1952. 00:09:07.19 Then there were three facts that added to this very intense development 00:09:14.21 in January and February of 1953, 00:09:17.17 and I can almost follow it from minute to minute. 00:09:19.24 So what were these things? 00:09:21.25 Well, Rosalind Franklin had clarified that there were two forms of DNA. 00:09:29.03 And both of them could crystallize, 00:09:31.07 but the B form was a little wetter, there was more water, 00:09:35.14 It didn't crystallize as well, so she was mostly concerned with the A form. 00:09:40.05 But what she didn't understand was that they were two forms of the same molecule. 00:09:44.27 And if she had really decided to work on the B form, 00:09:51.28 she might have made even better headway 00:09:54.23 than what she did, but she did achieve very important data. 00:09:58.10 Watson and Crick knew about this because Perutz, 00:10:05.01 who was on the review committee to look at the data from King's College, 00:10:11.07 leaked the information that was in the report from December 1952. 00:10:16.01 [00:10:16.02 ]Now that has been very much discussed and Perutz himself has said that 00:10:20.07 well, I was immature, and I didn't... I mean it wasn't secret material, so I shared it. 00:10:24.22 But the other thing was something that happened, and that was in January, 00:10:31.23 because then Watson was visiting King's College and then he was shown this picture. 00:10:36.15 And it had been taken by Rosalind Franklin and her collaborator Gosling, 00:10:41.16 as named on this, and it's a very, very special picture, and when Watson saw this, 00:10:50.10 and he received this information via Wilkins, 00:10:54.03 he immediately understood this must be a double helix. 00:10:59.02 And of course Crick who was the one who really knew structure, 00:11:02.06 could really support that and conclude that it was 00:11:04.21 a double helix with the two helices running in the opposite direction. 00:11:09.01 Here is the point in history where we are never going to know the truth. 00:11:14.09 Because it says in many books that this picture was taken from Rosalind Franklin 00:11:18.19 without her knowledge. And the family still believes that that is the case. 00:11:23.10 But you have the other side of the version 00:11:25.08 where it says in the annotated book of the Double Helix 00:11:29.00 where it says that Franklin gave this picture to Wilkins as a gift and he could use it. 00:11:35.19 Personally I think the truth is somewhat in between these two. 00:11:40.01 I don't think really that the photograph was really stolen from Franklin. 00:11:44.08 If that had been the case, she would have been much more upset. 00:11:47.24 And she was person of considerable temperament. 00:11:50.22 And later on this picture 51 has been used to illustrate 00:11:55.04 the structure of DNA, and used by Crick in reviews. 00:11:58.27 There is even a play that's called Photograph 51 00:12:02.15 that really describes the fascinating life of Rosalind Franklin. 00:12:07.04 And I might as well mention that already here she worked on DNA for 27 months, 00:12:14.05 and then she left and started to study viruses. 00:12:17.25 Did some major contributions to study of virus structure. She really pioneered that work. 00:12:23.13 And then in 1956, she was diagnosed with ovarian cancer, 00:12:29.14 and she died in 1958. She was never nominated for a Nobel Prize. 00:12:33.11 But she was clearly a person who could have been a very strong candidate for that. 00:12:40.12 So this photograph, it went well, but the third thing that was very, very crucial, 00:12:46.04 was that in order to make the model building... to build the models, 00:12:53.12 Watson had to cut out the different nucleotides, 00:12:57.12 and he used Davidson's textbook, which everyone was using. 00:13:00.00 That was the chemistry of its time. 00:13:02.28 And then there was another person, again in the same room 00:13:07.16 where they were at Cavendish laboratories, Jerry Donohue, 00:13:09.24 who was from California, like people called him. 00:13:12.08 And Jerry Donohue for some reason said that I think you shouldn't use the structure 00:13:16.06 that is there in Davidson's textbook. 00:13:19.00 You should use the other form of bases, 00:13:20.16 and I can just say Watson said, oh what are the two form of bases? I mean, he didn't know much of chemistry. 00:13:26.11 But he decided not to use the enol form, but upon the advice of Jerry Donohue he used the keto form. 00:13:33.26 And that was what really solved the whole thing 00:13:37.04 because then one could build the final model. 00:13:40.15 And that is when it all converged. 00:13:42.10 And the final model was the really, let's say the identification of the structure 00:13:49.02 was in the morning of February 28, 1953. 00:13:52.18 And here's a few days later with Watson and Crick in a very famous picture 00:13:57.28 illustrating what the model looks like. 00:13:59.29 Now once one had this model, 00:14:02.11 everything became very clear because here was a beautiful simple molecule 00:14:09.07 that when it replicated, retained the same structure in its semi-conservative replication. 00:14:15.19 It also had these bases that could come in any order, 00:14:22.08 and therefore could represent an information carrying device. 00:14:28.02 And of course, very soon after this one started to study what could the genetic language be. 00:14:34.22 And since there are four bases and there are twenty amino acids, 00:14:40.23 clearly it was not enough to have just pairs of bases, 00:14:44.22 because that would not suffice for all the amino acids, 00:14:47.03 so there must be triplets and then 00:14:49.04 progressively one could interpret the language 00:14:53.18 that nature has used ever since life started to develop... 00:14:58.03 this DNA designed life that started to develop, and this was some 3.8 billion years ago. 00:15:05.19 So the impact was absolutely enormous, 00:15:10.05 and the story goes of course that on that February 28th, 00:15:13.15 Watson and Crick went down to the pub that they used to visit after their day's work, 00:15:18.27 and said that we have found the molecule of life. 00:15:21.23 Probably it's a good story. No one has managed to substantiate that. 00:15:25.24 And one, for example, one has interviewed Odile Crick, while she was still alive 00:15:30.14 and asked her was something special on that February 28? 00:15:35.00 And she said, well, normally when Crick came home 00:15:38.03 there was always some wild story about the great discovery that he had made 00:15:41.10 because he was always a hypomaniac person, 00:15:45.07 but on this day he had some very good reasons to be that. 00:15:48.03 So here's Watson receiving the prize in 1962, 00:15:52.10 from the hands of His Majesty the King. 00:15:55.04 And he was the third youngest Nobel laureate in Physiology or Medicine, 00:16:04.00 the youngest being Frederick Banting, 00:16:07.06 and then Josh Lederberg were also younger than Watson. 00:16:11.24 32 and 33 years each. But Watson was 34 years old. 00:16:16.18 And had the privilege of a long, rich life 00:16:19.24 in which he could come back and recollect and discuss that February. 00:16:25.02 But before that perhaps, let me illustrate that I have tried to introduce in different chapters 00:16:34.03 in this book that I have just recently published some small haikus. 00:16:42.03 And the haiku that related to the chapter that discusses DNA simply reads, 00:16:44.15 The double helix 00:16:46.11 Eternity in a string 00:16:48.05 Symmetry well used 00:16:49.20 And I want to emphasize the eternity 00:16:53.12 because this is the language that has been used ever since 00:16:56.11 the genetic language was invented 00:16:59.21 or when life originated in the world.

Talk Overview

Erling Norrby takes us through the history of the discovery of DNA structure, starting in the 1940s and ending in 1962 when the Nobel Prize in Physiology or Medicine was awarded to Watson, Crick, and Wilkins. Determining the structure of DNA involved contributions from biologists, chemists, and physicists, and was not without controversy and competition. Here, Norrby tells the story of how these scientists’ knowledge came together to make one of the greatest discoveries in all of biology.

Speaker Bio

Erling Norrby was a professor of Virology for 25 years at the Karolinska Institute, the School of Medicine in Stockholm, and during these years he was heavily involved in the selection process for the Nobel Prize in Physiology or Medicine. He then served as Permanent Secretary at the Royal Swedish Academy of Sciences for six… Continue Reading

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This material is based upon work supported by the National Science Foundation and the National Institute of General Medical Sciences under Grant No. MCB-1052331.

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